Specific 1-(2-chloroethyl)-1-nitrosoureas, e.g. carmustine (BCNU; 1,2-bis-(2-chloroethyl)-nitrosourea), lomustine (CCNU; 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) and semustine (Methyl-CCNU; 1-(2-chloroethyl)-3-(4-methyl-cyclohexyl)-1-nitrosourea) are used as chemotherapeutic agents for the treatment of a number of experimental and clinical tumours (1).
It is generally known, however, that these compounds have several serious toxic effects, e.g. damaging effects on liver, kidney, lung organs, and also bone marrow depression, neurotoxicity and gastrointestinal toxicity (1-4).
One new compound of the same type, chlorozotocin or 2-/3-(2-chloroethyl)-3-nitrosoureido/-D-glucopyranose, which is under clinical evaluation, has been shown to possess decreased bone marrow toxicity (5), but the other types of toxicities are still evident, e.g. liver and lung toxicity (6, 7).
It is also generally known that after some time tumours tend to develop resistance to the anticancer therapy employed, thus rendering the therapy without curative effect.
Thus, the need exists for new and improved chemotherapeutic agents of this type, either or both with increased antitumour activity and decreased toxicity.